Singapore scientists show targeting cancer stem cells can prevent gastric cancer recurrence

19 DECEMBER 2025

SINGAPORE — Scientists from A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB) have identified the specific cells responsible for gastric cancer's tendency to return after treatment. The study also demonstrated that eliminating these cells stops tumours from growing, even in advanced disease that has spread to other organs.

The study, published in Science, reveals that a protein called Aquaporin-5 (AQP5) marks these cells. When the researchers selectively eliminated AQP5-expressing cells in laboratory models, tumours shrank and did not return.

The challenge of gastric cancer recurrence

Gastric cancer remains a significant health burden in Singapore and across Asia, where incidence rates are among the highest in the world. More than two-thirds of patients are diagnosed at advanced stages, contributing to poor survival outcomes.

One of the greatest challenges is that the disease frequently recurs. A patient may undergo surgery or chemotherapy and show no signs of remaining disease, only for the cancer to reappear months or years later, often having spread to organs such as the liver or lungs.

Scientists have long suspected that a small population of cells survives treatment and regenerates the tumour. These "cancer stem cells" are thought to resist conventional therapies, allowing the disease to return even after the visible tumour has been removed.

Previous attempts to identify gastric cancer stem cells using other protein markers, such as CD44 or CD133, yielded inconsistent results. These markers often appeared on healthy cells as well or did not fully account for tumour behaviour.

Identifying and eliminating cancer stem cells

The A*STAR team discovered that AQP5 reliably marks the cancer stem cells in gastric tumours. Aquaporins are proteins that form channels in cell membranes to control the movement of water into and out of cells. While AQP5 was previously known to mark stem cells in healthy gastric tissue, this study shows it also identifies the specific cells responsible for driving tumour growth, spread, and recurrence.

Importantly, AQP5 does more than simply mark these cells; it actively contributes to their aggressive behaviour.

The researchers found that cells with AQP5 were capable of forming new tumours, while cells without AQP5 rarely did so. Most significantly, when they used a targeted method to eliminate only the AQP5-expressing cells, tumours stopped growing or shrank entirely and did not recur. This held true even for cancers that had spread to other organs.

"Gastric cancer's high recurrence rate has long posed a challenge for clinicians," said Prof Nick Barker, Senior Principal Scientist at A*STAR IMCB. "These findings give us a defined target to pursue. We are now working to develop therapies against AQP5-expressing cells that could offer patients a better chance of lasting remission."

Towards targeted therapies for gastric cancer

The discovery builds on Prof Barker's 2020 research, published in Nature, which identified AQP5 as a marker of stem cells in healthy gastric tissue. These normal stem cells are responsible for the continuous renewal of the stomach lining. The current study shows that when these stem cells become cancerous, they retain AQP5, making it a reliable way to identify the cells that drive tumour growth.

The findings point to AQP5 as a potential target for new gastric cancer treatments. The research team is now developing AQP5-specific antibodies and evaluating drug candidates, with the aim of conducting preclinical studies. Any therapy would need to be tested in clinical trials before it could be used in patients. This process typically takes many years.

The study was led by Prof Nick Barker, Senior Principal Scientist at A*STAR IMCB, with Dr Grace Lim and Swathi Yada as co-first authors. Dr Lim was awarded the 2024 L'Oréal-UNESCO For Women in Science fellowship for her work on gastric cancer stem cells. Prof Barker is an internationally recognised authority in gastrointestinal stem cell biology whose 2007 discovery of LGR5 as a marker of intestinal stem cells, published in Nature, established foundational tools now used in cancer research worldwide. He has been recognised among the world's top 2% most-cited scientists for six consecutive years (2020–2025) in the Stanford University–Elsevier global ranking.

Study Citation: Lim HYG^†, Yada S^†, Murakami K, Lee BTK, Sagiraju S, et al. AQP5: A functional gastric cancer stem cell marker in mouse and human tumors. Science (2025). DOI: 10.1126/science.adr2428

^†Co-first authors

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Owen Sia
Corporate Communications
Agency for Science, Technology and Research (A*STAR)
Tel: +65 6517 7866
Email: owen_sia@a-star.edu.sg

About A*STAR Institute of Molecular and Cell Biology (A*STAR IMCB)

A*STAR Institute of Molecular and Cell Biology is a premier research institute whose mission is to harness biology for transformational bio-therapeutics and diagnostics. With a strong emphasis on collaboration with stakeholders across the ecosystem in Singapore, A*STAR IMCB aims to achieve scientific excellence and continues to nurture the next generation of scientists in order to create growth and enhance lives. For more information about IMCB, please visit www.a-star.edu.sg/imcb.

About the Agency for Science, Technology and Research (A*STAR)

The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STAR’s R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.

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